With Men's Y Chromosome, Size Really May Not Matter

The human Y chromosome (left) holds the code for "maleness"; that's the X on the right.

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Originally published on July 29, 2014 8:05 am

Basic biology has it that girls are girls because they have two X chromosomes — the things inside cells that carry our genes. Boys are boys because they have one X and one Y. Recently, though, there's been a lot of debate in scientific circles about the fate of that Y chromosome — the genetic basis of maleness.

Very early in the evolution of the Y chromosome, explains Dr. David Page, a geneticist at the Massachusetts Institute of Technology, something pretty dramatic happened: The ancestral Y lost most of its genes. And scientists basically ignored the little that was left.

"The Y chromosome was essentially written off as the runt of the human genome," Page says, "as a sort of genetic wasteland that didn't really merit anyone's serious attention."

When the Y did get any attention, it wasn't good news. Some scientists, like geneticist Jennifer Graves at La Trobe University in Melbourne, Australia, speculated that the Y might be destined to just keep sort of ... rotting away.

"As soon as it becomes a male-determining chromosome, then the rot sets in," Graves says. "That's kind of the kiss of death for that chromosome," meaning the Y chromosome could be headed toward oblivion — completely disappear.

But other scientists, including Page, say: Not so fast. Step away from my Y chromosome.

"I've really spent the better part of my career defending the honor of the Y chromosome in the face of insults of this sort," Page says.

For the Y, size really doesn't matter, he says. Page has done a detailed analysis of the chromosome's evolution and says the string of genes has been solidly stable now for millions of years.

"The idea that the Y chromosome might disappear altogether, possibly taking men with it — I think that idea has now been firmly dismissed," he says.

In fact, the relatively few precious genes that are left on the Y look like they're special — very special.

"There are genes on the Y chromosome that are active throughout every nook and cranny of the body," Page says. "The skin, the blood, the brain, the lungs — you name it. They look to be sort of global entrepreneurs within the human genome. They are sort of master regulators."

Still, Graves remains skeptical.

"I don't think that one can assume that just because they're there and they do something useful they'll be there forever and ever," she says. "A small accident could tip it over the edge, or the evolution of a new sex-determining system that works better."

Graves says she is always surprised by the ferocious reaction she gets to any suggestion that the male chromosome might be vulnerable.

"I've been accused in print of being, you know, a ball-breaking feminist," she says. "Well, no — not really. I'm just pointing out that things change, and evolution is wonderful, and it can do things lots of different ways."

Graves has a theory about why the reaction is so intense, especially among men.

"There's some deep-seated insecurity that men have about their Y chromosomes," she says, half-joking. "When I give lectures about the demise of the Y chromosome, I see men sort of hunching up into this protective stance as though I'm physically attacking them."

And there's a twist in all this. Even if the Y chromosome is here to stay, that may be something of a double-edged sword for men. Even if those master genes on the Y chromosome are important, they may also help explain why men are more prone to certain diseases than women are — and tend to live shorter lives.

Jan Dumanski, of Uppsala University in Sweden, and his colleagues recently reported, for example, a possible link between the Y chromosome and an increased risk for lots of cancers. He sees the human Y chromosome as "the Achilles' heel for men."

"It's making us men," Dumanski says, "but also causing us some trouble when we are getting older."

Clearly, our relationship with Y continues to be complicated. And it's not all about size.

Copyright 2014 NPR. To see more, visit http://www.npr.org/.

Transcript

UNIDENTIFIED MAN 1: All right, boy.

ARI SHAPIRO, HOST:

Time to talk men.

UNIDENTIFIED MAN 2: Dude.

UNIDENTIFIED MAN 3: Dude.

UNIDENTIFIED MAN 2: Dude, you the man.

UNIDENTIFIED MAN 3: No, you the man.

UNIDENTIFIED MAN 2: Like, you the man.

(SOUNDBITE OF FILM, "HAMLET")

UNIDENTIFIED ACTOR: (As Prince of Denmark) What a piece of work is a man.

SHAPIRO: Four hundred years since Shakespeare penned that last line, and we're still marveling at what makes men men. Today, enduring maleness. First, the Y-chromosome. The one that makes men men on a fundamental level. Among scientists, there's debate about its future. NPR's Rob Stein reports on the notion that the Y could one day be drowned out.

ROB STEIN, BYLINE: The world we live in sounds something like this.

(CHANTING)

UNIDENTIFIED WOMEN: Women, women, women.

STEIN: A world of women.

(CHANTING)

UNIDENTIFIED MEN: Men, men, men, men, men, men, men, men.

STEIN: And men. Women. Men. Women. Men. Now imagine this.

(SINGING)

UNIDENTIFIED WOMEN: Women, women, women, women...

STEIN: A world in which there are no men. I know what you're thinking. What's the chance of that?

(LAUGHTER)

UNIDENTIFIED WOMAN: Are you sure? (Laughing).

STEIN: Well, some scientists say if you look at our genes and how the rest of the world works, then maybe, just maybe. Now before we get into why we're talking about this, we probably need a quick refresher on basic human biology. There are those things called chromosomes. They're structures inside cells that carry our genes. Girls are girls because they have two X-chromosomes. Boys are boys because they have one X and one Y-chromosome.

DAVID PAGE: The Y-chromosome is what causes a baby to become a boy.

STEIN: That's David Page. He studies the Y-chromosome at MIT. And he says very early on in the evolution of the Y-chromosome, something pretty dramatic happened.

PAGE: The Y-chromosome lost almost all of the genes that were on that ancestral chromosome.

STEIN: Leaving behind the smallest chromosome in the human genetic blueprint. So for years, scientists just kind of ignored it.

PAGE: The Y-chromosome was essentially written off as the runt of the human genome, as a sort of genetic wasteland that didn't really merit anyone's serious attention.

STEIN: And when the Y did get anyone's attention, it wasn't good news. Some scientists, like Jennifer Graves at La Trobe University in Australia, speculated that the Y might be kind of rotting away.

JENNIFER GRAVES: As soon as it becomes a male determining chromosome, then the rot sets in. Then that's kind of the kiss of death for that chromosome.

STEIN: Meaning the Y could be headed toward oblivion.

GRAVES: At the rate at which the Y-chromosome has been losing genes, at this rate, the Y-chromosome's going to disappear.

STEIN: But scientists like Page take offense and say, not so fast. Step away from my Y-chromosome.

PAGE: I've really spent, you know, the better part of my career defending the honor of the Y-chromosome in the face of insults of this sort.

STEIN: Page says this is a case where size really doesn't matter. He just published a big new analysis of the Y-chromosome. It shows the Y's been rock-solid stable now for millions of years. It's not going anywhere anytime soon.

PAGE: The idea that the Y-chromosome might disappear altogether, possibly even taking men with it, I think that idea has now been firmly dismissed.

STEIN: And, he says, in fact, the relatively few precious genes that are left on the Y look like they're special, very special.

PAGE: There are genes that are active throughout every nook and cranny of the body - the skin, the blood, the brain, the lungs, you name it. They look to be sort of global entrepreneurs within the human genome, sort of master regulators.

STEIN: But remember Jennifer Graves? She's still skeptical. The Y's not necessarily safe just because it's been stable for a while and may have a bunch of supposedly important genes.

GRAVES: I don't think that one can assume that just because they're there and they do something useful they'll be there forever and ever. A small accident could dip it over the edge.

STEIN: So what would happen? There would be no men?

GRAVES: It's a possibility. You could envision a future population that reproduces itself by cloning.

STEIN: Or by doing artificial insemination with, say, sperm made in a petri dish from stem cells. Another possibility is that the gene that makes males could simply jump ship, and move to a different chromosome. That's already happened to some rather odd species of rodents.

GRAVES: There's a group of rodents called spiny rats in Japan. So there's three different species. One still has a Y-chromosome, although it's a really weird Y-chromosome. And the other two have lost their Y-chromosomes.

STEIN: Or maybe we evolve a different way to reproduce, like some reptiles in Australia.

GRAVES: We work on one lizard. It's called a Dragon lizard. A beautiful thing with sort of green horns.

STEIN: Sometimes they have males and females.

GRAVES: And it can do sex.

STEIN: After males wave their arms, bob their heads, and even change colors to woo females.

GRAVES: But if it's hot, everybody's a female.

STEIN: Really? All female?

GRAVES: A lot of people kind of like the idea of this Amazonian tribe of women only.

STEIN: Grave says she's always surprised by the reaction she gets to any suggestion that the human male chromosome might be vulnerable.

GRAVES: I've been accused in print of being, you know, a ball-breaking feminist. I think, well, no, not really. I'm just pointing out that things change, and evolution is wonderful and it can do things lots of different ways.

STEIN: She has a theory about why the reaction is so intense, especially among men.

GRAVES: There's some deep-seated insecurity that men have about their Y-chromosomes. (Laughing). It's almost like an appendage. I mean, when I give lectures about the demise of the Y-chromosome, I see men sort of hunching up into these protective stances like I'm physically attacking them. (Laughing).

STEIN: And there's a twist - even if men do hold on to their Y-chromosomes, it may turn out to be kind of a double-edged sword. Those master genes on the Y-chromosome might be important, but they may also help explain why men tend to live shorter lives than women. Jan Dumanski of Uppsala University in Sweden and his colleagues, for example, recently reported a possible link between the Y-chromosome and an increased risk for lots of cancers.

JAN DUMANSKI: We think that human chromosome Y is the Achilles heel for men. It's making us men but also causing us some trouble when we are getting older.

STEIN: So if the world is going to continue to have males with Y-chromosomes, men may have to come to terms with the fact that even their relationship with their Y-chromosome is, well, complicated. Rob Stein, NPR News.